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| | ==Crystal structure of SHP1 catalytic domain with JAK1 activation loop peptide== | | ==Crystal structure of SHP1 catalytic domain with JAK1 activation loop peptide== |
| - | <StructureSection load='4gs0' size='340' side='right' caption='[[4gs0]], [[Resolution|resolution]] 1.80Å' scene=''> | + | <StructureSection load='4gs0' size='340' side='right'caption='[[4gs0]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4gs0]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GS0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GS0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4gs0]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GS0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GS0 FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=FTY:DEOXY-DIFLUOROMETHELENE-PHOSPHOTYROSINE'>FTY</scene>, <scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7961Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HCP, PTP1C, PTPN6, SHP-1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FTY:DEOXY-DIFLUOROMETHELENE-PHOSPHOTYROSINE'>FTY</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] </span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4gs0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gs0 OCA], [https://pdbe.org/4gs0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gs0 RCSB], [https://www.ebi.ac.uk/pdbsum/4gs0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gs0 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4gs0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gs0 OCA], [http://pdbe.org/4gs0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gs0 RCSB], [http://www.ebi.ac.uk/pdbsum/4gs0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gs0 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PTN6_HUMAN PTN6_HUMAN]] Modulates signaling by tyrosine phosphorylated cell surface receptors such as KIT and the EGF receptor/EGFR. The SH2 regions may interact with other cellular components to modulate its own phosphatase activity against interacting substrates. Together with MTUS1, induces UBE2V2 expression upon angiotensin II stimulation. Plays a key role in hematopoiesis.<ref>PMID:11266449</ref> [[http://www.uniprot.org/uniprot/JAK1_HUMAN JAK1_HUMAN]] Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway. Kinase partner for the interleukin (IL)-2 receptor. | + | [https://www.uniprot.org/uniprot/PTN6_HUMAN PTN6_HUMAN] Modulates signaling by tyrosine phosphorylated cell surface receptors such as KIT and the EGF receptor/EGFR. The SH2 regions may interact with other cellular components to modulate its own phosphatase activity against interacting substrates. Together with MTUS1, induces UBE2V2 expression upon angiotensin II stimulation. Plays a key role in hematopoiesis.<ref>PMID:11266449</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Tyrosine phosphatase|Tyrosine phosphatase]] | + | *[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Protein-tyrosine-phosphatase]] | + | [[Category: Large Structures]] |
| - | [[Category: Alicea-Velazquez, N L]] | + | [[Category: Alicea-Velazquez NL]] |
| - | [[Category: Boggon, T J]] | + | [[Category: Boggon TJ]] |
| - | [[Category: Jakoncic, J]] | + | [[Category: Jakoncic J]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Hydrolase-transferase complex]]
| + | |
| - | [[Category: Phosphatase domain]]
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| - | [[Category: Protein-protein complex]]
| + | |
| Structural highlights
Function
PTN6_HUMAN Modulates signaling by tyrosine phosphorylated cell surface receptors such as KIT and the EGF receptor/EGFR. The SH2 regions may interact with other cellular components to modulate its own phosphatase activity against interacting substrates. Together with MTUS1, induces UBE2V2 expression upon angiotensin II stimulation. Plays a key role in hematopoiesis.[1]
Publication Abstract from PubMed
SHP-1 (PTPN6) is a member of the SHP sub-family of protein tyrosine phosphatases and plays a critical role in the regulation of the JAK/STAT signaling pathway. Previous studies suggested that SHP-1 contains a PTP1B-like second phosphotyrosine pocket that allows for binding of tandem phosphotyrosine residues, such as those found in the activation loop of JAK kinases. To discover the structural nature of the interaction between SHP-1 and the JAK family member, JAK1, we determined the 1.8A co-crystal structure of the SHP-1 catalytic domain and a JAK1-derived substrate peptide. This structure reveals electron density for only one bound phosphotyrosine residue. To investigate the role of the predicted second site pocket we determined the structures of SHP-1 in complex with phosphate and sulfate to 1.37A and 1.7A, respectively, and performed anomalous scattering experiments for a selenate-soaked crystal. These crystallographic data suggest that SHP-1 does not contain a PTP1B-like second site pocket. This conclusion is further supported by analysis of the relative dephosphorylation and binding affinities of mono- and tandem-phosphorylated peptide substrates. The crystal structures instead indicate that SHP-1 contains an extended C-terminal helix alpha2' incompatible with the predicted second phosphotyrosine binding site. This study suggests that SHP-1 defines a new category of PTP1B-like protein tyrosine phosphatases with a hindered second phosphotyrosine pocket.
Structure-guided studies of the SHP-1/JAK1 interaction provide new insights into phosphatase catalytic domain substrate recognition.,Alicea-Velazquez NL, Jakoncic J, Boggon TJ J Struct Biol. 2013 Jan 4. pii: S1047-8477(12)00343-7. doi:, 10.1016/j.jsb.2012.12.009. PMID:23296072[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Keilhack H, Muller M, Bohmer SA, Frank C, Weidner KM, Birchmeier W, Ligensa T, Berndt A, Kosmehl H, Gunther B, Muller T, Birchmeier C, Bohmer FD. Negative regulation of Ros receptor tyrosine kinase signaling. An epithelial function of the SH2 domain protein tyrosine phosphatase SHP-1. J Cell Biol. 2001 Jan 22;152(2):325-34. PMID:11266449
- ↑ Alicea-Velazquez NL, Jakoncic J, Boggon TJ. Structure-guided studies of the SHP-1/JAK1 interaction provide new insights into phosphatase catalytic domain substrate recognition. J Struct Biol. 2013 Jan 4. pii: S1047-8477(12)00343-7. doi:, 10.1016/j.jsb.2012.12.009. PMID:23296072 doi:http://dx.doi.org/10.1016/j.jsb.2012.12.009
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